The elucidation of genes regulating the complex behavioral phenotypes related to drug abuse including initial drug sensitivity, tolerance, sensitization, chronic use and relapse have only recently been amenable to molecular analyses. The application of quantitative trait loci (QTL) methods has allowed the mapping of genes regulating these polygenic traits. Moreover, transgenic mouse and inducible mutagenesis techniques allow investigations into the impact of single gene manipulations on drug-induced alterations of behavioral and physiological function. QTLs have been localized for morphine preference, alcohol sensitivity, tolerance, and withdrawal. While there is considerable knowledge pertaining to the neurobiological circuitry underlying drug reinforcement, little is known about the genetic polymorphisms that may mediate individual differences in genes regulating important neural substrates regulating reinforcement and reward. Heterogeniety of phenotype makes gene mapping particularly difficult in the human population for alcohol and substance abuse. By integrating current knowledge of genetic factors that may predispose individuals to drug use and abuse with biological and molecular studies in animal models, advancement will be made. The conference will cover important breakthroughs in the mapping of genes for alcohol, cocaine, nicotine, and opiate dependence and abuse. A workshop presenting genetic methods that have not been widely applied to the complex issues of alcohol and substance abuse will supplement presentations and discussion of recent data. This workshop will include the use of chemically-induced mutations in mamalian and invertebrate organisms and RNA differential gene expression techniques.